Mann B, Gratchev A, Böhm C, Hanski M L, Foss H D, Demel G, Trojanek B, Schmidt-Wolf I, Stein H, Riecken E O, Buhr H J, Hanski C
Department of General Surgery, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Germany.
Br J Cancer. 1999 Mar;79(7-8):1262-9. doi: 10.1038/sj.bjc.6690202.
Colorectal carcinoma cells have recently been shown to express Fas ligand (FasL). This ligand could allow the tumour cells to evade activated tumour-infiltrating lymphocytes (TILs) by inducing their apoptosis and would thus promote tumour survival and possibly metastasis formation. To test this hypothesis in vivo we analysed the expression of FasL mRNA and protein in paired tissue samples of normal colonic mucosa (N), primary colorectal carcinomas (T) and their metastases (M) from a total of 21 patients by four different methods. Additionally, the presence and activation status of infiltrating lymphocytes, which might contribute to the total amount of FasL in the tissue, was determined by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) in the same samples. The frequency of FasL detection was 30-40% in T and was 60-100% in M, depending on the sensitivity of the method. Simultaneously, the amount of CD25 mRNA, used as a measure of the number of activated TILs, was in 90% of patients lower in M than in T. The increased frequency of FasL detection in liver metastases was therefore not due to the presence of activated TILs. We conclude that metastasizing subpopulations of colorectal tumour cells express FasL more frequently than the primary carcinomas and may be able to eliminate activated TILs in vivo via Fas/FasL-induced apoptosis or other hitherto unknown mechanisms.
最近研究表明,结肠直肠癌细胞可表达Fas配体(FasL)。该配体可通过诱导活化的肿瘤浸润淋巴细胞(TILs)凋亡,使肿瘤细胞得以逃避TILs的杀伤,从而促进肿瘤存活并可能促进转移形成。为在体内验证这一假说,我们采用四种不同方法,分析了来自21例患者的正常结肠黏膜(N)、原发性结肠直肠癌(T)及其转移灶(M)的配对组织样本中FasL mRNA和蛋白的表达情况。此外,还通过半定量逆转录聚合酶链反应(RT-PCR)测定了同一组织样本中浸润淋巴细胞的存在情况及其活化状态,这些淋巴细胞可能对组织中FasL的总量有影响。根据检测方法的灵敏度,FasL在T中的检测频率为30%-40%,在M中的检测频率为60%-100%。同时,作为活化TILs数量指标的CD25 mRNA量,在90%的患者中,M中的含量低于T。因此,肝转移灶中FasL检测频率的增加并非由于活化TILs的存在。我们得出结论,结肠直肠肿瘤细胞的转移亚群比原发性癌更频繁地表达FasL,并且可能能够通过Fas/FasL诱导的凋亡或其他迄今未知的机制在体内清除活化的TILs。